The objectives of this work are: a) to study the nature of the chemical changes in enzyme molecules in cells of old animals which render the molecules inactive; b) to study the physiological significance of the accumulation of inactive enzyme molecules in cells of senescent animals. 1. The characteristics of an NADPH-dependent enzymatic system of liver which restores activity to partially inactive superoxide dismutase (SOD) from old animals will be further investigated. Understanding of the mode of action of this system will enable identifying the age-related alterations in SOD. 2. Purified "young" and "old" SOD and aldolase B will be subjected to amino acid and peptide analysis in an attempt to identify modified amino acid residues in altered "old" molecules. 3. The possibility that the accumulation of altered molecules is due to defects in the degradation system will be further explored. The rate of disposal of puromycyl-peptides from livers of C57 B1 mice of various ages will be investigated. 3H puromycin will be injected and the disappearance of label from peptides of various sizes will be determined. 4. The effect of peroxides and hypotonic conditions on erythrocytes of various cellular and donor ages will be investigated. The response of the erythrocytes of various ages to these stresses will be related to the levels of glucose-6P-dehydrogenase, SOD, catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX). Correlation of the results with the mean life span of the erythrocytes will be sought. 5. The response to inflammagens in the lung and pleural and peritoneal cavities of young and old animals will be tested and correlated with the activity levels of SOD, GPX, CAT and indoleamine dioxygenase.